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D-serine is the primary N-methyl D-aspartate receptor (NMDAR) coagonist at synapses, regulating NMDAR activity and neurotoxicity. Inhibiting D-serine offers a novel neuroprotective strategy.

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Area of Science:

  • Neuroscience
  • Neurochemistry

Background:

  • N-methyl D-aspartate receptors (NMDARs) are crucial for synaptic plasticity and function.
  • Glycine and D-serine are known coagonists of NMDARs, but their specific roles are debated.

Purpose of the Study:

  • To review recent data on the roles of D-serine and glycine in NMDAR regulation and neurotoxicity.
  • To clarify the distinct functions of D-serine and glycine as NMDAR coagonists.

Main Methods:

  • Review of recent scientific literature on NMDAR coagonists.
  • Analysis of data concerning D-serine and glycine origins, release mechanisms, and functional roles.

Main Results:

  • D-serine is synthesized and released by both neurons and astrocytes.
  • Neuronal and glial D-serine are essential for long-term potentiation and synapse formation.
  • D-serine acts as the physiological coagonist at synaptic NMDARs, while glycine acts extrasynaptically.

Conclusions:

  • D-serine is identified as the principal synaptic NMDAR coagonist.
  • D-serine mediates synaptic NMDAR activation and neurotoxicity, acting as a key neurotransmitter or neuromodulator.
  • Inhibiting D-serine synthesis or release presents a promising neuroprotective therapeutic strategy.